The Pharmacology Core will continue to provide analytical, drug metabolism and pharmacokinetic services in support of project goals that seek to relate drug or drug metabolite concentrations to treatment outcome. We specifically propose to support four projects in the renewal period. For example, we will (a) assist in the implementation of targeting of CY metabolites CEPM and HCY in a Phase III trial to evaluate the effect on nonrelapse mortality, organ injury and engraftment; (b) support the search for a relationship between actual exposure to active metabolites of CY and organ toxicity in preparative regimens combining BU and CY ; (c) support a comparison of fludarabine (FLU)/BU as an alternative to BU/CY in patients with CML receiving HLA matched sibling grafts, with results provided to and perhaps modifying the approach; and (d) provide continued pharmacokinetic support to Phase I/II and Phase III trials of mofetil mycophenolate and rapamycin, respectively, to prevent graftversus-host disease. In some instances, we propose to identify the causes of interpatient variability in actual exposure to active compounds at a given dose of drug.